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Thrombocytopenia signals multiorgan system failure in acute liver failure


 

FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY

References

In patients with acute liver failure (ALF), decreasing platelet counts after hospital admission signaled systemic inflammation and a greater likelihood of systemic complications, such as high-grade hepatic encephalopathy, cardiovascular collapse, the need for liver transplant, and death, according to researchers.

Patients with systemic inflammatory response syndrome (SIRS) had significantly lower platelet counts at admission, compared with those without SIRS, and their platelet counts decreased dramatically (from 182 plus or minus 27 times 109/L on admission to 103 plus or minus 3.20 times 109/L on day 6) compared with stable platelet counts in patients without SIRS. For days 2-7 postadmission, lower platelet counts were associated with high-grade hepatic encephalopathy, as well as the need for vasopressor support and renal replacement therapy (P less than or equal to .001 for all).

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“We hypothesize that the decrease in platelet count represents an integral event in the pathogenesis of the ALF syndrome rather than a nonspecific marker of suppressed bone marrow production. Further studies will be needed to prove the pivotal role of platelets in mediating the proinflammatory and prothrombotic features of the ALF syndrome,” wrote Dr. R. Todd Stravitz, professor of medicine, section of hepatology, Virginia Commonwealth University, Richmond, and his colleagues (Clin Gastroenterol Hepatol. 2016 Feb 25. doi: 10.1016/j.cgh.2015.09.029).

Results showed that SIRS and multiorgan system failure (MOSF) were more closely linked to a decrease in platelet counts than to an increase in the international normalized ratio (INR), a laboratory marker for liver injury. The INR was similar in patients with and without SIRS, in high-grade and low-grade hepatic encephalopathy, and in patients with and without requirements for vasopressor support and renal replacement therapy (indicators of MOSF). Given that both platelet counts and INR were associated with prognosis, the investigators suggest that these laboratory parameters may reflect different types of injury, with INR signaling primary liver injury and platelets reflecting the severity of systemic inflammation secondary to liver injury.

Platelet counts varied according to outcome on day 21. Spontaneous survivors had higher mean platelet counts than patients who underwent liver transplant, and patients who died had the lowest platelet counts. Platelet counts in spontaneous survivors decreased from day 1 to 2, then subsequently recovered; platelets decreased progressively in patients who underwent liver transplant or died. The INR trend over time according to 21-day outcome was similar to that of platelet counts.

The retrospective study evaluated data from 1598 patients who enrolled in the ALF Study Group from 1998 to 2012. The mean age was 41 years, 76% were Caucasian, and 70% were female. Nearly one-half of participants (47%) had ALF due to acetaminophen overdose, 85% had at least one positive element of SIRS on admission, 32% required vasopressors, 33% required renal replacement therapy, and 50% developed high-grade (3 or 4) hepatic encephalopathy. In total, 47% of patients recovered without liver transplant, 24% underwent liver transplant, and 32% died.

The mechanism underlying development of thrombocytopenia in patients with ALF is poorly understood. Previous findings by the investigators showed that platelet-derived, prothrombotic microparticles increased in proportion to SIRS severity, and concentration of microparticles increased in parallel with laboratory markers of poor outcome. Current results suggest the converse to be true as well: platelet counts decreased in proportion to the severity of SIRS, the development of MOSF and poor outcome at 21 days.

The researchers proposed that deficiencies in the number of platelets or in liver-derived, prohemostatic coagulation factors may be compensated by systemic inflammation. Increased levels of platelet-derived microparticles in patients with ALF may overcompensate for thrombocytopenia due to a nearly 40-fold higher prothrombotic potential in tissue factor–dependent assays, compared with healthy control populations.

The findings point to the importance of platelet count in signaling impending complications in patients with ALF.

Dr. Stravitz and his coauthors reported having no disclosures.

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